serotonin

Serotonin is synthesized in the body, but its precursor, tryptophan, is not. Tryptophan must be supplied in the diet in order for this neurotransmitter to be manufactured. Approximately 1% of dietary tryptophan is converted into serotonin. While serotonin synthesis is relatively simple, the metabolism and incorporation of tryptophan into serotonin generating cells is a complex process. There are multiple metabolic pathways for incorporating and storing tryptophan. Tryptophan reaches serotonin generating cells by binding to serum albumin, because tryptophan itself is largley nonpolar and has low solubility in the bloodstream. The binding of tryptophan to serum albumin is very pH dependent and physiological conditions such as acidosis or alkyosis can disrupt tryptophan transport.

Serotonin, being a neurotransmitter, exerts its effects by its interaction with a receptor. Stimulation of serotonin receptors leads to a number of different cell processes, depending on the receptor type. Some lead to the turnover of cellular lipids such as phosphoinositol phosphate and diaglyceride formation. Others trigger adenylate cyclase which then results in a cascade of cell signalling events.

Serotonin levels can be assayed directly in post-mortem autopsies or by looking for downstream degraded products in the CSF and urine. 5-HIAA in particular is often found in these two fluids. Because of the widespread use of serotonin in many different physiological processes from neurochemistry to digestion, understanding how serotonin levels correlate with physical and psychological pathologies is an area of intense study. Efforts to understand how serotonin levels may correlate with propensity for suicide and comitting violent crime are yielding interesting results.

see also:

• Why does tryptophan make you drowsy?
• serotonin and suicide
• serotonin and violent crime to be noded

Many different serotonin receptors have been discovered; they have been divided into subtypes:

• 5-HT_1A: activation of these receptors inhibits firing of serotonin neurons and lowers the release of serotonin in the prefontal cortex; this receptor controls mood and is implicated in depression.
• 5-HT_1B: controls the release of other neurotransmitters, and connected to aggression, implicated in learning and memory dysfunctions.
• 5-HT_1D: the drug Sumatripan (Imitrex) is a 5-HT1D agonist used in treating migraine and cluster headaches.
• 5-HT_1E
• 5-HT_1F: possibly linked to migraine headaches.


• 5-HT_2A: increased density of this subtype can indicate an increased risk of suicide.
• 5-HT_2B: 2B & 2C subtypes have an inhibitory effect on the mesolimbic and nigrostriatal dopamine pathways; stimulation of the 2B receptor reduces anxiety and tension, and this receptor is found throughout the body.
• 5-HT_2C: see above; may be responsible for regulation of cerebral spinal fluid, as well as sleep.


• 5-HT_3A: 3A & 3B subtypes are linked to vomiting; ondansetron, granisetron, dolasetron, palonesetron, and alosetron are all antiemetic 5-HT3 antagonists.
• 5-HT_3B: see above.


• 5-HT_4A: 4A & 4B are connected to dopamine function, and may also be responsible for inducing tachycardia.
• 5-HT_4B: see above.


• 5-HT_5A
• 5-HT_5B


• 5-HT₆: involved in cognitive functions such as learning and memory.


• 5-HT_7A
• 5-HT_7B
• 5-HT_7C
• 5-HT_7D

Serotonin's chemical structure:

                H
                 \
           H  H   N
            \  \ / \
 H   H       C--C   H
  \   \     / \  \
   O   C   C   H  H
    \ / \\/ \\
     C   C   C
    ||   |   /\
     C   C--N  H
    / \ //   \
   H   C      H
        \
         H